THE ROLE OF VESICULAR TRANSPORT PROTEINS IN SYNAPTIC TRANSMISSION ANDNEURAL DEGENERATION

Classical neurotransmitters are synthesized in the cytoplasm, so they require transport into secretory vesicles for regulated exocytotic rel ease. Previous work has identified distinct vesicular transport activi ties for the different classical transmitters, and all depend on the H +-electrochemical gradient across the vesicle membrane but differ in t he extent to which they rely on the chemical and electrical components of this gradient. Drugs that interfere with vesicular amine transport have implicated this activity in psychiatric disease. Selection for a cDNA encoding vesicular amine transport in the neurotoxin MPP(+) also implicates the activity in Parkinson's disease. Molecular cloning of vesicular monoamine transporters shows sequence similarity to bacteria l antibiotic resistance proteins, supporting a role for transport in d etoxification and defining a novel mammalian gene family that now also includes a transporter for acetylcholine. Current work focuses on the mechanism of transport and the role that regulation of activity and i ts subcellular localization have in transmitter release, behavior, and neural degeneration.